Method for predicting the response to a treatment

Abstract

The invention is related to a method of predicting the response to a treatment with a HER inhibitor in a patient comprising the steps of assessing a biomarker or a combination of biomarkers selected from the group consisting of amphiregulin, an epidermal growth factor, a transforming growth factor alpha, and a HER2 biomarker in a biological sample from the patient and predicting the response to the treatment with the HER inhibitor in the patient by evaluating the results of the first step. Further uses and methods wherein these markers are used are disclosed.

1 . A method of predicting the response of a patient to treatment with a HER dimerization inhibitor comprising the steps of:
 (a) determining the expression level one or more biomarker proteins with one such biomarker protein being transforming growth factor alpha;   (b) determining whether the expression level assessed in step (a) is above or below a certain quantity that is associated with an increased or decreased clinical benefit to a patient; and   (c) predicting the response to the treatment with the HER inhibitor in the patient by evaluating the results of step (b).   
     
     
         2 . A method according to  claim 1  wherein, in step (a), in addition to the expression level of transforming growth factor alpha, the level of expression of one or more biomarker proteins, selected from the group consisting of epidermal growth factor, amphiregulin, and HER2, is also determined. 
     
     
         3 . A method according to  claim 2  wherein, in step (a), the level of expression of transforming growth factor alpha is determined in combination with the level of expression of: epidermal growth factor; HER2; or both amphiregulin and HER2. 
     
     
         4 . A method according to  claim 1  wherein the HER dimerization inhibitor inhibits heterodimerization of HER2 with EGFR or HER3. 
     
     
         5 . A method according to  claim 1  wherein the HER dimerization inhibitor is an antibody. 
     
     
         6 . A method according to  claim 1  wherein the HER dimerization inhibitor is the antibody 2C4. 
     
     
         7 . A method according to  claim 1  wherein the patient is a cancer patient. 
     
     
         8 . A method according to  claim 1  wherein the patient is a breast cancer, ovarian cancer, lung cancer or prostate cancer patient. 
     
     
         9 . A method according to  claim 1  wherein the level of expression of said biomarker protein or proteins is assessed by detecting the level of expression of fragments thereof. 
     
     
         10 . A method according to  claim 1  wherein the level of expression said biomarker or biomarkers is determined using a reagent which specifically binds with the biomarker protein or the fragment thereof or the combination of biomarker proteins or the fragments thereof. 
     
     
         11 . A method according to  claim 10  wherein said reagent is selected from the group consisting of an antibody, a fragment of an antibody, and an antibody derivative. 
     
     
         12 . A method according to  claim 1  wherein a biomarker protein is the extracellular domain of HER2. 
     
     
         13 . A method according to  claim 12  wherein said extracellular domain extracellular domain of HER2 has a molecular mass of approximately 105,000 Daltons. 
     
     
         14 . A method according to  claim 1  wherein the amino acid sequence of the transforming growth factor alpha biomarker protein is SEQ ID NO: 3 
     
     
         15 . A method according to  claim 2  wherein the amino acid sequence of the amphiregulin biomarker protein is SEQ ID NO: 1, the amino acid sequence of the epidermal growth factor biomarker protein is SEQ ID NO: 2, the amino acid sequence of the transforming growth factor alpha biomarker protein is SEQ ID NO: 3, and the amino acid sequence of the HER2 biomarker protein is SEQ ID NO: 4. 
     
     
         16 . A method according to  claim 1  wherein the amount of transforming growth factor alpha is determined in a biological sample of blood serum and the quantity that is associated with an increased clinical benefit to a patient is within the range between 2.0 to 10.0 pg/ml of transforming growth factor alpha. 
     
     
         17 . A method according to  claim 2  wherein the amounts of transforming growth factor alpha, amphiregulin, epidermal growth factor, and HER2 marker proteins are determined in a biological sample of blood serum and the quantities that are associated with an increased clinical benefit to a patient are within the range of between 2.0 to 10.0 pg/ml of transforming growth factor alpha, between 6 to 15 pg/ml of amphiregulin, between 100 to 250 pg/ml of epidermal growth factor, and between 12 to 22 ng/ml of HER2 marker proteins. 
     
     
         18 . A method according to  claim 2  wherein the amounts of transforming growth factor alpha, amphiregulin, epidermal growth factor, and HER2 marker proteins are determined in a biological sample of blood serum and the quantities that are associated with an increased clinical benefit to a patient are about 3.5 pg/ml of transforming growth factor alpha, about 12 pg/ml of amphiregulin, about 150 pg/ml of epidermal growth factor, and about 18 ng/ml of HER2 marker proteins.